PROJECT SUMMARY/ ABSTRACT This is a resubmission for a Midcareer Investigator Award in Patient-Oriented Research (K24). The applicant, Dr. Richard Souza, is a clinician-scientist, Associate Professor in Physical Therapy and Rehabilitation Science and the University of California, San Francisco. Throughout his career, Dr. Souza has built upon his clinical background through detailed and comprehensive studies on the influence of loading mechanics on knee and hip osteoarthritis (OA). These studies have used biomechanical methods such as motion capture systems, and strength assessment through dynamometry, and have characterized disease status and progression using advanced quantitative MRI metrics including T1? and T2 relaxation time mapping of knee and hip cartilage and semi-quantitative lesion scoring. Combining his background in musculoskeletal biomechanics with the world- renowned research team in the Department of Radiology and Biomedical Imaging at UCSF, Dr. Souza has been able to uncover key biomechanical variables that contribute to the earliest changes in the OA process. These efforts have resulted in a recently completed R01 on Joint Contact Mechanics in Knee OA, and a recently funded MPI R01 on hip OA progression. Understanding the predictive capability of lower extremity joint biomechanics to identify disease progression has been the driving force of Dr. Souza?s work. Furthermore, Dr. Souza is currently a Co-Investigator on a study evaluating the influence of weight changes on knee OA progression (PI: Link), and has also recently completed a Center of Research Translation grant (MPIs: Majumdar & Lane) that provided the key preliminary data for the funded R01 project of hip OA progression. These activities and projects have led to a broad multidisciplinary team focused on advancing our understanding of OA in patient oriented research. The current application requests funding (50% salary support) for 5 years to support the protected time necessary to conduct the proposed patient oriented research and to expand opportunities for mentoring within the UCSF community. This protected time will allow Dr. Souza to continue to lead a productive research group and maintain minimal teaching and administrative responsibility at the Departmental and University levels. Dr. Souza will also obtain additional training in advanced MR and PET MR analysis and enable participation in the Training in Clinical Research (TICR) program. There are plentiful opportunities to expand the work Dr. Souza has begun, and extremely high potential for clinical break-through in this important area of clinical research.